Hospital-acquired (or nosocomial) pneumonia (HAP) and ventilator- associated pneumonia (VAP) remain important causes of morbidity and mortality despite improvements in prevention, antimicrobial therapy, and supportive care

Pneumonia types — Pneumonia is frequently categorized based on site of acquisition

●   Hospital-acquired (or nosocomial) pneumonia (HAP) is pneumonia that occurs 48 hours or more after admission to the hospital and did not appear to be incubating at the time of admission.

●   Ventilator-associated pneumonia (VAP) is a type of HAP that develops in intubated patients on mechanical ventilation for more than 48 hours. VAP also includes HAP that occurs within 48 hours of extubation.

●   Non-ventilator-associated HAP (NV-HAP) refers to HAP that develops in hospitalized patients who are not on mechanical ventilation nor underwent extubation within 48 hours before pneumonia developed. NV-HAP can be divided into patients that ultimately require mechanical ventilation (VHAP) due to the pneumonia versus those that do not. VHAP is associated with particularly poor clinical outcomes.

Ø  PATHOGENESIS:

 The pathogenesis of HAP and VAP is related to the number and virulence of micro-organisms entering the lower respiratory tract and the response of the host (eg, mechanical, humoral, and cellular host defenses).

The primary route of infection of the lungs is through microaspiration of organisms that have colonized the oropharyngeal tract (or, to a lesser extent, the gastrointestinal tract) . Approx 45 percent of healthy subjects aspirate during sleep and an even higher proportion of severely ill patients aspirate routinely. Although frequently regarded as partially protective, the presence of an endotracheal tube facilitates aspiration of oropharyngeal secretions and bacteria into the lungs.

Hospitalized patients often become colonized with microorganisms acquired from the hospital environment, and as many as 75 percent of severely ill patients will be colonized within 48 hours.

An additional mechanism of inoculation in mechanically ventilated patients is direct contact with environmental reservoirs, including respiratory devices and contaminated water reservoirs. Disposable tubing used in respiratory circuits or tracheostomy or endotracheal tubes may become contaminated in the process of routine nursing care or via the (contaminated) hands of hospital personnel. Such contamination can occur despite rigorous cleaning of ventilator equipment.

In addition, the near sterility of the stomach and upper gastrointestinal tract may be disrupted by alterations in gastric pH due to illness, medications, or enteric feedings. For this reason, much attention has been paid to the possible adverse effect of ulcer prophylaxis regimens that raise the gastric pH.

Less frequently, pneumonia results from inhalation of infectious aerosols or from bacteremia originating in a distant focus.

Ø  MICROBIOLOGY:

 The most common organisms are Staphylococcus aureus (including methicillin- resistant S. aureus) and Pseudomonas aeruginosa.

Other common causes - aerobic gram-negative bacilli (eg, Escherichia coli, Klebsiella pneumoniae, Enterobacter spp, Acinetobacter spp)  and  gram-positive  cocci (eg, Streptococcus spp).

Also may be due to viruses in general medical and surgical patients and both viruses and fungi in immunocompromised patients.

Ø  RISK FACTORS:

 The most significant risk factor for HAP is intubation. Other risk factors include:

●   Older age

●   Chronic lung disease

●   Depressed consciousness

●   Aspiration

●   Chest or upper abdominal surgery

●   Agents that increase gastric pH (H2 blockers, antacids, proton pump inhibitors [PPIs])

●   Previous antibiotic exposure, especially broad spectrum

●   Reintubation or prolonged intubation

●   Mechanical ventilation for acute respiratory distress syndrome

●   Frequent ventilator circuit changes

●   Total opioid exposure

●   Multiple trauma

●   Paralysis

●   Number of central venous catheter placements and surgeries

●   Use of muscle relaxants or glucocorticoids

●   The presence of an intracranial pressure monitor

●   Malnutrition, chronic renal failure, anemia, Charlson Comorbidity Index, previous hospitalization

Role of gastric pH — There is an increased incidence of HAP when the gastric pH is increased with the use of H2 blockers, antacids, or PPIs. Avoid agents that raise gastric pH in patients who are not at high risk of developing a stress ulcer or stress gastritis.

Ø  DIAGNOSIS :

 The clinical diagnosis of HAP and VAP is difficult in part because the clinical findings are nonspecific. The 2016 IDSA/ATS guidelines for the management of HAP and VAP recommend a clinical diagnosis based upon a new lung infiltrate plus clinical evidence that the infiltrate is of infectious origin, which includes the new onset of fever, purulent sputum, leukocytosis, and decline in oxygenation.

While the clinical features described above support the diagnosis of HAP or VAP, no individual sign or symptoms nor any combination of signs and symptoms have been found to be highly sensitive or specific for diagnosis. As an example, the presence of a new or progressive radiographic infiltrate plus at least two of three clinical features (fever >38ºC, leukocytosis or leukopenia, and purulent secretions) has a 69 percent sensitivity and 75 percent specificity for VAP.

Cultures of pulmonary secretions (sputum, endotracheal aspirates, bronchoalveolar lavage) are also prone to false positives and false negatives. When compared with histology, quantitative endotracheal aspirate cultures had a pooled sensitivity of 48 percent and positive predictive value of 81 percent ; quantitative bronchoalveolar lavage cultures had a sensitivity of 75 percent and positive predictive value of 77 percent.

Ø  TREATMENT :

 EMPIRIC THERAPY-

Timing of antibiotics — Once nvHAP or VAP is suspected clinically, microbiological specimens should be obtained as soon as possible in all patients. In patients with signs of septic shock or rapidly progressive organ dysfunction, antimicrobial therapy should be started as soon as possible. If the diagnosis is uncertain and the patient is not in sepsis or septic shock, then it appears to be safe and potentially beneficial to gather more data and await culture results before treating.

Regimens — Dosing will need to be adjusted in those with renal dysfunction. When available, choice of antibiotics should be guided based on local antibiogram resistance rates.

o  No risk factors present — suggest a regimen that has activity against Pseudomonas, other gram-negative bacilli, and methicillin- susceptible S. aureus (MSSA). Preferred intravenous empiric antibiotic regimens include one of the following:

o  

●   Piperacillin-tazobactam 4.5 g IV every 6 hours

● Cefepime 2 g IV every 8 hours

However, levofloxacin 750 mg IV daily may be preferred if there is a high suspicion for Legionella spp infection and local resistance rates of S. aureus, P. aeruginosa, and other gram-negative bacilli to fluoroquinolones are low . The ATS/IDSA guidelines also include imipenem and meropenem as options, but we generally reserve these agents for patients with a high likelihood of infection with an extended-spectrum beta-lactamase (ESBL)-producing gram-negative bacillus or for patients in units where local antibiograms favor these agents over other broad- spectrum beta-lactams.

o  Risk factors for MDR gram-negative bacilli

No history of carbapenem-resistant pathogens — suggest one of the following :

●   Meropenem 1 g IV every eight hours

● Imipenem 500 mg IV every six hours

Patients at risk of seizures from imipenem (eg, renal insufficiency, underlying central nervous system [CNS] disease) should be closely monitored or alternative beta- lactams should be used.

History of carbapenem-resistant pathogens — suggest empiric monotherapy with one of the following agents:

●   Ceftazidime-avibactam 2.5 g IV every eight hours

● Ceftolozane-tazobactam 3 g IV every eight hours

● Imipenem-cilastatin-relebactam 1.5 g IV every six hours

● Meropenem-vaborbactam 4 g every eight hours

If the beta-lactam beta-lactamase agents listed above are not available and there is a high suspicion for carbapenem-resistant gram-negative bacilli, then the addition of one of the following agents along with a carbapenem is a reasonable alternative:

●   Tobramycin 5 to 7 mg/kg IV daily

● Colistin 300mg colistin base activity (CBA) loading dose followed by 150 mg CBA every 12 hours

● Aztreonam 2 g IV every eight hours

● Levofloxacin 750 mg IV or orally daily

● Ciprofloxacin 750 mg IV every 12 hours or 400mg orally every eight hours

o  Risk factors for MRSA — recommend either linezolid or vancomycin for infections suspected or proven to be due to MRSA .

Preferred agents — For patients with VAP or nvHAP who have risk factors for MRSA, we suggest adding one of the following agents to the patient's empiric therapy regimen:

●   Linezolid 600 mg IV every 12 hours, which may be administered orally when the patient is able to take oral medications.

●   Vancomycin dosing as summarized in the following table

DURATION OF THERAPY: Suggest treating most patients with nvHAP or VAP for seven days, in agreement with the 2016 ATS/IDSA guidelines and the combined 2017 European and Latin American guidelines on HAP and VAP . Seven days appears to be as effective as longer durations in most circumstances and may reduce the emergence of resistant organisms.

For selected patients with metastatic infection, gram-positive bacteremia, slow response to therapy, immunocompromise, and pyogenic complications such as empyema or lung abscess, the duration of therapy should be individualized and courses longer than seven days may be warranted.

Monitoring serial procalcitonin levels can help guide the decision to discontinue antibiotics. While the optimal approach to using procalcitonin in patients with HAP or VAP has not been determined, a low or declining procalcitonin level (eg, <0.25 ng/mL or ≥80 percent decrease from peak) in a patient who has clinically improved on antibiotics provides additional reassurance that antibiotics can be safely stopped.

CONVERSION TO ORAL ANTIBIOTICS:

Switch to oral therapy when they are hemodynamically stable, clinically improving, and able to tolerate oral medications. If a pathogen has been identified, the choice of antibiotic for oral therapy should be based on the organism's susceptibility pattern. If a pathogen has not been identified, the oral antibiotic selected should be based on an appropriate de-escalation approach and generally can exclude coverage for MRSA and P. aeruginosa. All oral antibiotics selected for the treatment of pneumonia should have good lung penetration

PREVENTION

 The Society for Healthcare Epidemiology of America (SHEA) and the Infectious Diseases Society of America (IDSA) issue updated practice recommendations to reduce the risk of VAP and NV-HAP (table 2).

Essential practices that are recommended by SHEA/IDSA for preventing VAP and NV-HAP in all acute care hospitals include avoiding intubation and preventing reintubation when possible (eg, using noninvasive ventilation or high-flow oxygen by nasal cannula instead), minimizing sedation through the use of sedative protocols, implementing ventilator liberation protocols, maintaining and improving physical conditioning, elevating the head of the bed, providing oral care with toothbrushing but without chlorhexidine, and changing ventilator circuits only if visibly soiled or malfunctioning.

The following discussion will review some of the modalities that have been evaluated for preventing VAP.

Preventing aspiration — Aspiration is a major predisposing mechanism for both HAP and VAP. Elevating the head of the bed, minimizing sedation, draining subglottic secretions in ventilated patients, maintaining endotracheal tube airway cuff pressure (20 to 30 cm H2O), and application of positive end-expiratory pressure are measures that have been proposed to minimize aspiration.

Patient positioning — Supine positioning appears to predispose to aspiration and the development of HAP, particularly in patients receiving enteral nutrition. The head of the bed should therefore be elevated to 30 to 45° .While no effect of positioning on duration of mechanical ventilation or mortality has been demonstrated, it seems prudent to preferentially place intubated patients in the semirecumbent position unless contraindicated.

Subglottic drainage — Drainage of subglottic secretions that pool above the endotracheal tube cuff may lessen the risk of aspiration of secretions around the cuff and thereby decrease the incidence of VAP.

Gastric volume monitoring — It has long been standard clinical practice to monitor patients’ gastric residual volume at regular intervals and/or prior to increasing the infusion rate of gastric tube feeding, with the hope of minimizing the risk of unrecognized gastric fluid accumulation and vomiting resulting in pneumonia. However, several studies have shown that measurement of gastric residuals correlates poorly with aspiration risk and is associated with a decrease in calorie delivery.

Decontamination of the oropharynx and digestive tract — Decontamination of the oropharynx and/or digestive tract may reduce the incidence of pneumonia in critically ill patients by decreasing colonization of the upper respiratory tract. Potential methods used include antiseptics in the oropharynx, selective decontamination of the oropharyngeal tract (SOD) with nonabsorbable antibiotics applied in the oropharynx, and selective decontamination of the digestive tract (SDD) with nonabsorbable antibiotics applied to the oropharynx and administered orally, with or without intravenous antibiotics.

Selective decontamination of the digestive tract — Selective decontamination of the digestive tract (SDD) refers to use of nonabsorbable antibiotics applied to the oropharynx and administered orally, with or without four days of intravenous antibiotics. Examples of antimicrobials included in oral and gastric tube regimens include colistin, tobramycin, and nystatin. The intravenous agent is typically a third- generation cephalosporin or a quinolone.